Genetic landscape of meningioma

Abstract

Meningioma is the most common intracranial tumor, arising from arachnoid cells of the meninges. Monosomy 22 and inactivating mutations of NF2 are well-known genetic alterations of meningiomas. More recently, mutations in TRAF7, AKT1, KLF4, SMO, and PIK3CA were identified by next-generation sequencing. We here reviewed 553 meningiomas for the mutational patterns of the six genes. NF2 aberration was observed in 55 % of meningiomas. Mutations of TRAF7, AKT1, KLF4, PIK3CA, and SMO were identified in 20, 9, 9, 4.5, and 3 % of cases, respectively. Altogether, 80 % of cases harbored at least one of the genetic alterations in these genes. NF2 alterations and mutations of the other genes were mutually exclusive with a few exceptions. Clinicopathologically, tumors with mutations in TRAF7/AKT1 and SMO shared specific features: they were located in the anterior fossa, median middle fossa, or anterior calvarium, and most of them were meningothelial or transitional meningiomas. TRAF7/KLF4 type meningiomas showed different characteristics in that they occurred in the lateral middle fossa and median posterior fossa as well as anterior fossa and median middle fossa, and contained a secretory meningioma component. We also discuss the mutational hotspots of these genes and other genetic/cytogenetic alterations contributing to tumorigenesis or progression of meningiomas.

Diagnosis and Predictors of Treatment Outcomes in Meningiomas with Atypical or Anaplastic Histology

“…In our series those cases with atypical or anaplastic subtypes at primary surgery, demonstrated better response to Simpson grade I resection and adjuvant radiotherapy than those cases that progressed from grade I subtype. Some genetic alteration related to progression, as previously reported in literature, can probably explain different evolution among tumors expressing the same histology like in these series 8,10,11 .…”

Molecular Testing of Brain Tumor

“…Sixty percent of the sporadic meningiomas have mutations in TRAF7 , KLF4 , AKT1 , SMO , and PIK3CA [50-52]. Among them, mutations in TRAF7 and KLF4 are found in secretory-type meningiomas and mutations in TRAF7 / AKT1 / PIK3CA are found in meningothelial and transitional-type meningiomas [52,53]. Mutations in TRAF7 are the most common genomic aberrations and are found in 12%–15% of sporadic meningiomas, preferentially fibrous and transitional subtype, which are found concurrently with mutations in KLF4 , AKT1 , or PIK3CA , but are mutually exclusive with mutations in SMO and neurofibromatosis type 2 ( NF2 ) [53].…”

“…NF2 -associated meningiomas have mutations in NF2 . Atypical and anaplastic meningiomas usually have mutations in TERTp or marked copy number aberrations and loss of CDKN2A /2B [53]. These findings demonstrate that tumors are genetic disorders and that certain mutations can represent different biological behaviors and result in different prognoses.…”

Metastatic meningioma presenting as a malignant soft tissue tumour

“…It could be argued that the possibility of malignant meningioma should have been suspected earlier given that the morphological and immunohistochemical findings were so typical of this tumour with focal, occasionally whorled collections of strongly EMA+ tumour cells being typical of a meningotheliomatous meningioma [1, 2]. It should be noted that in more diagnostically challenging cases certain genetic/cytogenetic abnormalities such as inactivating mutations of NF2, monosomy 22, as well as specific alterations in gene expression, may also be useful in establishing the diagnosis of metastatic meningioma [31]. …”